Antibacterial material

ABSTRACT

An antibacterial material, a method of producing an antibacterial material and a method of inhibiting infection during the treatment of wounds using an antibacterial material. The antibacterial including a fibrous substrate impregnated with a carrier and a controlled release biocide dispersed through the carrier.

The present invention relates to antibacterial material and inparticular to material suitable as a dressing for wounds such asulcerated or burned tissue.

The invention has been developed primarily for use in dressing woundsand will be described hereinafter with reference to this application.However, it will be appreciated that the invention is not limited tothis particular field of use.

BACKGROUND OF THE INVENTION

The treatment and dressing of slow healing open wounds has been along-standing medical problem. Wound healing is an extremely complexbiological process and there are many factors to be taken into accountwhen considering the best possible treatment and dressing. Factors suchas risk of infection, time of treatment and patient comfort areimportant considerations.

Ulcers are a particularly painful form of slow healing wound and areoften difficult to treat due to underlying circulatory problems and thecontinuous risk of infection.

Ulcers are secreting skin wounds which produce exudates such as blood,pus and other wound fluids. These fluids can accumulate in the woundcavity and form a rich pool of nutrients which promotes bacterialgrowth. This, in turn, delays or prevents the healing process, or insome cases leads to further tissue damage or even the possibility ofsystemic life threatening infection.

It is would be desirable to allow such wounds to heal in a slightlymoist environment provided infection can be controlled and excess woundexudates can be removed to prevent blisters forming under the dressingor the dressing becoming embedded in the wound.

Examples of conventional dressings used to protect open wounds andpromote the healing process include traditional cloth, cotton or lintpads, non-adherent latex dressings and synthetic-algin coatings.

However, each of these dressings has drawbacks. Traditional dressings indirect contact with a wound can interfere with the healing process. Thisis particularly so with chronic ulcerated wounds because of the repeatedmechanical impact and interaction of the bandage with the fragile andpressure sensitive tissues within the wound. This problem is amplifiedby the repeated dressing changes which are often required. In many casesbecause there is new tissue growth the dressings adhere to the wound.This makes them difficult to remove without disrupting the healingprocess.

Non-adherent latex dressings have a high rate of allergic reaction.Along with some other types of conventional dressings, they are unableto absorb exuded fluids at a rate commensurate with the rate of fluidproduction by the wound or alternatively, their fluid holding capacityis not significant to allow long periods of time in contact with thewound. The progressive build up of bacteria then delays healing and mayalso produce unpleasant odours.

Algin type dressings are designed to avoid adhering to healing woundsand for easy removal. They present the appearance of being coated withjelly-like substance. While these may avoid adhering to a healing wound,they have a propensity to go mouldy when exposed to bacteria filledfluids for extended periods.

There is a need for a wound dressing that can continuously inhibit thegrowth of bacteria and be easily removed from the wound. Moreover, itwould be particularly desirable if the dressing could be left on thewound for a longer period of time than conventional dressings allow, inorder to avoid disrupting the wound and thus accelerating the healingprocess.

It is an object of the invention to overcome or ameliorate at least someof the disadvantages of the prior art, or to provide a usefulalternative.

DISCLOSURE OF THE INVENTION

The present invention relates to an antibacterial material, a method ofproducing an antibacterial material and methods of inhibiting infectionduring the treatment of wounds using the antibacterial material of thepresent invention.

According to a first aspect, the present invention provides anantibacterial material including:

-   -   a fibrous substrate impregnated with a carrier; and    -   a controlled release biocide dispersed through said carrier.

According to a second aspect, the present invention provides a processfor making an antibacterial material according to the first aspect, saidprocess including:

-   -   dispersing a controlled release biocide within a carrier to        provide an active carrier mixture; and    -   impregnating a fibrous substrate with said active carrier        mixture.

According to a third aspect, the present invention provides a method ofinhibiting infection during the treatment of wounds by applying anantibacterial material according to the first aspect to an affected skinarea on a patient.

According to a fourth aspect, the present invention provides use of anantibacterial material according to the first aspect in the manufactureof a dressing for inhibiting infection during the treatment of wounds.

The term “wound” includes tissue injury such as flesh wounds, mechanicalinjuries, ulcers, burns, open surgical wounds and lesions and also skinconditions such as acne.

Preferably, the substrate is paper. The carrier is preferably propyleneglycol, although other glycols may be used as carriers. Other suitablecarriers include alcohols.

Water based carriers may also be used. The biocide is preferablytriclosan, mobile within the carrier. Other suitable biocides may alsobe employed.

DETAILED DESCRIPTION OF THE INVENTION

A preferred embodiment of the invention will now be described, by way ofexample only, with reference to several examples.

The antibacterial material includes a fibrous substrate impregnated witha carrier having a controlled release biocide dispersed therethrough.Once the controlled release takes place, the biocide is mobile withinthe carrier so that it can travel to the site of action.

In its preferred embodiment, the substrate is a substantially cottoncellulose fibre blend, most preferably a soft sheet of open weave paper.In other embodiments, the substrate may be creped paper which has a highsurface area and increased stretch and flexibility. This enables thematerial in use to adapt readily to various configurations of thepatient.

The preferred paper substrate has sufficient wet strength to be pulledintact from a wound. However, in some embodiments the paper strength maybe selected to be disintegrable or dissolvable such that it can bewashed out of a wound if necessary. The weight of the substrate mayvary. Depending on particular requirements, the weight may be in therange of 50 to 200 gsm, more preferably in the range of 80 to 150 gsm,and most preferably in the range of 100 to 120 gsm.

Importantly, the biocide of the present invention is a controlledrelease biocide. In its preferred form, the biocide is encapsulated soas to be in a latent state capable of being activated by externalstimuli. The encapsulation for example, may be by means of polypropylenemicrospheres for instance. The external stimuli may include pressure orlight, in particular ultraviolet light. The level of antibacterialeffect may be varied by increasing or decreasing the amount of biocide.

When the biocide is released from encapsulation, it is taken up in thecarrier and dissolves therethrough.

The biocide itself is preferably triclosan. The preferred form ofencapsulated triclosan is that known under the trademark CANSAN®TCH.

Triclosan is non-toxic and non-allergenic to humans and inhibits thegrowth of bacteria such as E. coli Legionella or Staphylococcus and lowtitre viruses for example HIV. Preferably, the biocide is deactivated byblood serum such that it is effective in killing bacteria but has noeffect on humans. Preferably, the biocide is present in an amount of 10to 10,000 ppm of the carrier, depending upon the intended use.

For instance, use for dressings for non-serious wounds is 10-1,000 ppmbiocide, or 10-200 ppm biocide in even less serious cases. For seriouswounds, the concentration of biocide in the carrier is anywhere up toabout 3,000-6,000 ppm.

For other applications, such as handwipes, an amount of 10-100 ppm isfound to be appropriate. For air conditioning filters, a concentrationof about 100-500 ppm biocide in carrier is an appropriate concentration.These concentrations are those which would be used when the carrier isapplied at its preferred rate of 100 ml/m², or 1 litre of carrier per 10m². Appropriate adjustments to the concentration and rate of applicationto the substrate can be made to provide equivalent amounts of active ifrequired.

Surprisingly, when triclosan itself is applied to wounds or dressings ina conventional manner, it is rapidly degraded by serum and becomesineffective within a fairly short time.

The encapsulated biocide is dispersed through a carrier which ispreferably a glycol and most preferably propylene glycol. The carrier isapplied to the substrate at a rate of between 80 and 120 ml per squaremetre, and more preferably around 100 ml of the carrier is used persquare metre of the substrate. As well as acting as a carrier to takethe biocide to the necessary site of action, the humectant properties ofpropylene glycol keep the dressing damp and enable it to be easilyremoved from the wound.

The preferred method of adjusting the total amount of active in adressing or other article of the present invention is through varyingthe concentration of active in the carrier, rather than by thealternative procedure of varying the amount of carrier applied to thesubstrate.

Preferably, the fibrous substrate further includes strengtheningmaterial, such as a nylon resin and most preferably a Kymene resin.Typically, the strengthening resin is present in an amount of around0.01% to 0.06% by weight of the paper. Most preferably, the amount ofKymene resin is around 0.03%. The higher the amount of Kymene, theharder the paper. For example, air conditioning filters will have anamount of Kymene near the high end of the range as they require highstrength.

The antibacterial material of the present invention has a wide range ofpossible applications in the medical, dental and veterinary fields. Inits preferred form, the material is most suitable as a wound dressing.Unlike conventional dressings, which are changed daily, in its preferredform the material of the present invention can be left on the wound forextended periods of time, for example 3 to 4 days in some cases. Byminimising the number of dressing changes the wound has a better chanceof healing over a shorter period of total treatment time. The controlledrelease of active biocide kills bacteria or maintains a low bacterialpopulation throughout this time, thus inhibiting infection and reducingodour. It will be appreciated that the material is particularlyapplicable to the treatment of sensitive skin wounds such as burns andulcers.

Similarly, the material of the present invention may be adapted for useto inhibit infection during treatment of animal wounds such as injuriesto the front forelegs of horses. The skin in this area is particularlythin and prone to injury. Such injuries behave like ulcers in that theyare open and slow healing. The antibacterial material of the presentinvention can be used to accelerate the healing time of such wounds andthus return the horse more quickly to an active state.

The antibacterial material of the present invention has other uses inthe field of infection control.

One such alternative use is as a dressing during dental surgery. Gumwounds have a tendency to become ulcerated because of the favourableconditions for bacterial growth. Triclosan can be applied to the buccalmucosa without adverse effects.

Another use is as a surgical barrier, such as a bib for the protectionof surgeons, or as a sheet to protect patients. Any disruption to thesurgical barrier would result in immediate release of the antibacterialagent from the antibacterial material of the present invention.

The antibacterial material of the present invention may also be used towrap autoclaved instruments. The controlled release of active biocideensures sterility for longer periods of time than wrapping with standardplastic material which is susceptible to bacterial infection.

In other embodiments, the material of the present invention may beemployed as a wipe, including surface wipe to sterilise surfaces or ahand cleansing wipe to reduce the hand transfer of bacteria. It iswell-known that hand to mouth transfer of bacteria is a major cause ofbacterial infection. The material of the present invention may also beuseful in the treatment of acne. It will be appreciated that thebiocidal material of the present invention may be used with, forexample, waterproof backing materials or elastic backed stickingplasters.

In still further embodiments, the material of the present invention maybe used to combat airborne pathogens. Examples of this includeproduction of medical or other microbiologically protective masks formedfrom the antibacterial material.

The antibacterial material of the present invention may also be adaptedfor use as an air conditioning filter to combat Legionella or otherbacteria in the recirculated air within air conditioning ducts.Breakdown of the encapsulated biocide is proportional to the air flowvelocity through the filter. Thus, when air flow (and consequentlybacterial flux through the filter) is high, the amount of triclosanreleased is also high. When the air flow is off, there is not asignificant increase of airborne bacteria, and nor is there significantfurther release of triclosan. Thus, the biocide is delivered when it isneeded, and is not overproduced during times of low demand.

The antibacterial material of the present invention can be easily cut toany size, contributing to its wide range of applications.

By its very nature, the preferred material of the present invention isinherently sterile in its packaged form and is not fully activated untilplaced in use. This avoids the necessity for complex autoclavingprocedures. The packaged material of the present invention can betreated with gamma radiation in order to verify that the material issterile. Should any damage occur to the packaged material the damageitself releases the biocide to inhibit bacterial contamination.

Manufacture of the preferred material includes the step of producing anopen weave paper by conventional methods. However, before the finaldrying stage, the paper is sprayed with the carrier, which may be anaqueous carrier, an alcohol or a glycol, such as propylene glycolcontaining a dispersion of encapsulated triclosan at the requisiteconcentration for the intended purpose and then drying the paper withheat. For preference, roller drying is not used after the encapsulatedbiocide has been applied. The mechanical effect of packaging thedressing in a sealed package means that the paper of the presentinvention is self-sterilising when packaged. The material of the presentinvention thus avoids the need for expensive and complex autoclaving.

It will be appreciated that reduction in the amount of latex andplastics materials normally used in many of the above-mentionedapplications hugely reduces waste levels as well as costs.

The following examples illustrate preferred embodiments of the inventionadapted for particular applications.

EXAMPLE 1 Dressing for non-serious wounds

CANSAN ® TCH 1,000 ppm available triclosan Propylene glycol   100 mlOpen weave paper    1 m² Kymene resin 0.03% by weight of paper

EXAMPLE 2 Dressing for Serious Wounds

CANSAN ® TCH 3,000 ppm available triclosan Propylene glycol   100 mlOpen weave paper    1 m² Kymene resin 0.03% by weight of paper

EXAMPLE 3 Air Conditioning Filter

CANSAN ® TCH 500 ppm Propylene glycol 100 ml Open weave paper  1 m²Kymene resin 0.06% by weight of paper

EXAMPLE 4 Hand Wipe

CANSAN ® TCH  80 ppm Propylene glycol 100 ml Open weave paper  1 m²Kymene resin 0.03% by weight of paper

The following tests demonstrate the effectiveness of the preferredembodiment of the invention against several known forms of bacteria

EXAMPLE 5 Determination of the antimicrobial Activity of Paper Sheet,Treated with CANSAN® TCH

In Test 1, the antimicrobial activity of the different antibacterialPaper Sheets, treated with Cansan® TCH has been determined under agardiffusion test conditions.

In Test 2, the remaining antibacterial effect on hands after usage ofthe Cansan®TCH containing Paper Sheets have been tested under in-vivofingerprint test conditions against gram-positive and gram-negativebacteria.

EXAMPLE 5 Test 1

Samples: Paper Sheets

Cansan TCH Sprayed on Hand Sheets

Microbiological Evaluation

1. Determination of the Bacteriostatic Activity According to theBacterial Growth Inhibition Test.

Principle:

Discs with a diameter of 2 cm were punched out from the hand Sheets. Thediscs were applied on the top layer of the solidified agar containingthe bacteria. For the preparation of the top agar layer, from overnightcultures, a 1:100 (Staphyloccocus aureus and Micrococcus luteus) and a1:1000 (Escherichia coli) dilution were made and 3.5 ml of the dilutionswere added to 500 ml agar.

-   Test bacteria: Staphylococcus aureus ATCC 9144    -   Escherichia coli NCTC 8196-   Nutrient medium: Casein soy meal pepton agar (two layers of agar: 15    ml bottom layer without germs and 5 ml top layer with bacteria)-   Incubation: 18-24 hours at 37° C.

Results Staphylococcus aureus Escherichia coli Cansan TCH sprayed onATCC 9144 NCTC 8196 Sheets ZI VR ZI VR Sample 1: 10/10 5/4 5/5 4/4Original ENCAP-AM-37- 155A-1TLegend:ZI = zone of inhibition in mmVR = Vinson rating, for growth under the disc0 = strong growth (no activity)4 = no growth (good activity)L. J. Vinson et al. J. Pharm. Sci. 50, 827-830, 1961

EXAMPLE 5 Test 2

Finger Print Test

In Vivo Test for Determination of the Bacteriostatic Activity of aProduct that Contains an Antimicrobial Agent.

Samples: Paper Sheets

Cansan TCH Sprayed on Hand Sheets

-   Test bacteria: Staphylococcus aureus ATCC 9144    -   Escherichia coli NCTC 8196-   Nutrient medium: Casein soy meal pepton agar-   Incubation: 24 hours at 37° C.-   Principle:-   1. The hands were wetted for 15 sec. under running tap water.-   2. Hands were washed with a placebo soap, rinsed with tap water and    dried.-   3. Filter paper discs (2 cm diameter) soaked with ethanol were    placed in sterile plates. The fingertips were applied on the filter    paper discs for 30 sec. in order to allow a migration of Cansan due    to the excellent adsorption of ethanol. After 1 minute contact time,    the filter discs were dried in the plates and then placed in the    middle of agar plates containing the test germs (placebo sample).-   4. The hands were rinsed under running lukewarm tap water and    subsequently washed with the placebo soaps for 60 seconds.    Subsequently the later was washed off under running lukewarm tap    water. The hands have been dried with the test Paper Sheets for 1    minute.-   5. Ethanol soaked filter paper disks (2 cm diameter) were placed in    sterile plates and the same procedure as described under 3. has been    performed.-   6. The procedure after application of the test Sheets in order to    determine the activity of Cansan®TCH on the skin.-   7. The plates were incubated under optimal conditions according to    the germ's requirements on temperature and media.

Due to the diffusion of the antimicrobial ingredient from the filterinto the surrounding agar medium the growth of the test germs isinhibited in the diffusion zone.

For the assessment of the bacteriostatic activity, zones of inhibitionaround the filter discs are measured and given in mm.

EXAMPLE 5 Results

Cansan TCH Sprayed on Sheets Staphylococcus aureus Escherichia coli ATCC9144 NCTC 8196 Sample 1: ZI Vr ZI Vr Placebo (without Cansan) 0/0 0/00/0 0/0 Immediately after application 12/12 4/4 5/5 4/4

Each test was performed twice and both results are given in the table.

-   -   ZI=Zone of inhibition in mm    -   Vr=Vinson rating    -   0=strong growth (no activity)    -   4=no growth (good activity)

EXAMPLE 5 CONCLUSIONS

The Paper Sheets with Cansan® TCH showed good antibacterial effectsagainst gram-positive and gram-negative test bacteria under agardiffusion test conditions where the Paper Sheets were in direct contactwith the contaminated agar.

In order to show the effects under real in-vivo test conditions, anin-vivo finger print test has been performed. For this test the handswere washed with a placebo soap and dried with Cansan containing PaperSheets.

It was possible to show clear antibacterial effects on the hands, driedwith the “antibacterial Sheets”.

The results show clearly, that the use of Cansan® TCH containing PaperSheets can help to protect the hands from growth of pathogenic bacteriaand increase the hygiene on hands.

EXAMPLE 6 Preliminary Patient Test

A patient with a leg ulcer had the ulcer dressed with the antibacterialmaterial of the present invention. The dressing was changed after 3days, and the condition of the wound was observed after one week.

The natural healing of the wound was scored by a registered nurse asbeing 8/10.

A normal natural healing score for a leg ulcer dressed with aconventional dressing is expected to be around 4/10. While there is adegree of subjectivity in the scores, the preliminary test result isbelieved by the present applicants to be significant.

The dressing was readily removed, and did not adhere to the wound.

Conventional dressings would be expected to adhere to the wound tovarying degrees after only about one day, which is the life span of thedressing. The condition of the dressing was also examined and triclosanwas determined to be present. It was estimated that the dressing couldbe used for a further period, possibly being allowed to remain untouchedon the wound for as long as 4-5 days.

EXAMPLE 7 Preliminary Patient Test

A medical practitioner applied a dressing according to the presentinvention on the skin ulcers of six patients. The dressings of thepresent invention maintained a high standard of cleanliness of thewounds. After 2-3 weeks, the wounds exhibited accelerated healingrelative to comparable ulcers dressed with conventional dressings.

EXAMPLE 8 Preliminary Patient Test

A medical practitioner applied a dressing of the present invention to aminor burn as a result of scalding. The dressing contained 100 ppmCansan TCH in propylene glycol (applied at 100 ml per square metre)impregnated onto 120 gsm paper. After five days, the burn was almostcompletely healed, with only slight signs of scarring.

Although the invention has been described with reference to specifictests and examples, it will be appreciated by those skilled in the artthat the invention may be embodied in many other forms.

1. A method of inhibiting infection during the treatment of a wound byapplying an antibacterial material to an affected skin area on apatient, said antibacterial material including: a fibrous substrate,said fibrous substrate being impregnated with a carrier; and acontrolled release biocide dispersed through said carrier.
 2. A methodaccording to claim 1, wherein said biocide is mobile within saidcarrier.
 3. A method according to claim 1, wherein said substrate is asubstantially cellulose fibre blend.
 4. A method according to claim 3,wherein said substrate is paper.
 5. A method according to claim 4,wherein said paper has an open weave configuration.
 6. A methodaccording to claim 3, wherein the weight of said substrate is in therange of 50 to 200 gsm.
 7. A method according to claim 6, wherein theweight of said substrate is in the range of 80 to 150 gsm.
 8. A methodaccording to claim 7, wherein the weight of said substrate is in therange of 100 to 120 gsm.
 9. A method according to claim 3, wherein saidsubstrate dissolves in water.
 10. A method according to claim 1, whereinsaid biocide is in a latent state capable of subsequent activation byexternal stimulus.
 11. A method according to claim 10, wherein saidexternal stimulus is pressure.
 12. A method according to claim 10,wherein said external stimulus is light.
 13. A method according to claim12, wherein said light is ultraviolet light.
 14. A method according toclaim 10, wherein said biocide is encapsulated.
 15. A method accordingto claim 1, wherein said biocide is inactivated by blood serum.
 16. Amethod according to claim 1, wherein said biocide is non-allergenic tohumans.
 17. A method according to claim 1, wherein said biocide inhibitsthe growth of E. coli, Legionella or Staphylococcus.
 18. A methodaccording to claim 1, wherein said biocide is triclosan.
 19. A methodaccording to claim 18, wherein said triclosan is that known under thetrademark CANSAN®TCH.
 20. A method according to claim 1, wherein saidbiocide is present in an amount of 10 to 10,000 ppm.
 21. A methodaccording to claim 1, wherein said carrier transports said biocide tothe site of action.
 22. A method according to claim 1, wherein saidcarrier is a glycol.
 23. A method according to claim 22, wherein saidglycol is propylene glycol.
 24. A method according to claim 1, wherein100 ml of said carrier is used per m² of said substrate.
 25. A methodaccording to claim 1, wherein said material further includes a nylonresin.
 26. A method according to claim 25, wherein said nylon is aKymene resin.
 27. A method according to claim 1, wherein said wound isan ulcer.
 28. A method according to claim 1, wherein said wound is aburn.
 29. Use of an antibacterial material including a fibrous substrateimpregnated with a carrier, and a controlled release biocide dispersedthrough said carrier, in the manufacture of a dressing for inhibitinginfection during the treatment of wounds.
 30. A wound dressing includingan antibacterial material including a fibrous substrate impregnated witha carrier, and controlled release biocide dispersed through saidcarrier.
 31. A wound dressing according to claim 30, further including awaterproof backing material or an elastic-backed sticking plaster. 32.An antibacterial material suitable for use as a wound dressingincluding: a fibrous substrate having a weight of from 50 to 200 gsm,said fibrous substrate being impregnated with a carrier; and acontrolled release biocide dispersed through, and mobile within, saidcarrier.
 33. An antibacterial material according to claim 32, whereinsaid substrate is a substantially cellulose fibre blend.
 34. Anantibacterial material according to claim 33, wherein said substrate ispaper.
 35. An antibacterial material according to claim 34, wherein saidpaper has an open weave configuration.
 36. An antibacterial materialaccording to claim 35, wherein the weight of said substrate is in therange of 80 to 150 gsm.
 37. An antibacterial material according to claim36, wherein the weight of said substrate is in the range of 100 to 120gsm.
 38. An antibacterial material according to claim 33, wherein saidsubstrate dissolves in water.
 39. An antibacterial material according toclaim 32, wherein said biocide is encapsulated.
 40. An antibacterialmaterial according claim 32, wherein said biocide is triclosan.
 41. Anantibacterial material according to claim 40, wherein said triclosan isthat known under the trademark CANSAN®TCH.
 42. An antibacterial materialaccording to claim 32, wherein said biocide is present in an amount of10 to 10,000 ppm.
 43. An antibacterial material according to claim 32wherein said carrier is a glycol.
 44. An antibacterial materialaccording to claim 43, wherein said glycol is propylene glycol.
 45. Anantibacterial material according to claim 32, wherein 100 ml of saidcarrier is used per m² of said substrate.
 46. An antibacterial materialaccording to claim 32, wherein said material further includes a nylonresin.
 47. An antibacterial material according to claim 46, wherein saidnylon is a Kymene resin.
 48. A process for making an antibacterialmaterial according to claim 32, said process including: dispersing acontrolled release biocide within a carrier to provide an active carriermixture; and impregnating a fibrous substrate having a weight of from 50to 200 gsm with said active carrier mixture.